During the larval development of Drosophila, the number of cells in each imaginal disc increases about one thousand fold. The study of genetic mosaics produced by somatic recombination suggests that the temporal and spatial pattern of cell division is developmentally significant. The analysis of developmental mutants indicates that this pattern is genetically programmed and essential for normal development. These results raise several specific questions: what factors during embryogenesis stimulate imaginal disc cells to begin dividing? What mechanisms are responsible for the fact that clones derived from each imaginal disc precursor do not contain the same number of cells? Is there clustering of those cells with similar proliferation potential? What controls the rate of cell division and how do cells know when to stop dividing? We have isolated a large number of lethal mutants in which imaginal disc proliferation is profoundly abnormal. To begin answering the questions raised above, we have chosen those mutants for further study whose phenotypes suggest a basic defect either in the initiation pattern, rate, or termination of cell division. The effect of these mutations on the program of normal proliferation will be analyzed in vivo by mosaic analysis. Imaginal discs from temperature-sensitive alleles of these mutations will be cultured in vitro at permissive temperature and the effect on proliferation of shifts to restrictive temperature will be analyzed directly by autoradiography of histological sections of discs labeled with tritated thymidine and by measuring the fraction of labeled metaphase after pulse labeling with tritiated thymidine. The goal of this approach is to discover how the function of specific genes are integrated into a developmental program.